Dysregulation of microRNAs (miRNAs) plays a key role during the pathogenesis of chemoresistance in lung cancer (LCa). Previous study suggests that miR-324-5p may serve as a unique miRNA signature for LCa, but its role and the corresponding molecular basis remain largely explored. Herein, we report that miR-324-5p expression was significantly increased in cisplatin (CDDP)-resistant LCa tissues and cells, and this upregulation predicted a poor post-chemotherapy prognosis in LCa patients. miR-324-5p was further shown to impact CDDP response: Ectopic miR-324-5p expression in drug-naïve LCa cells was sufficient to attenuate sensitivity to CDDP and to confer more robust tumour growth in CDDP-challenged nude mice. Conversely, ablation of miR-324-5p expression in resistant cells effectively potentiated CDDP-suppressed cell growth in vitro and in vivo. Using multiple approaches, we further identified the tumour suppressor FBXO11 as the direct down-stream target of miR-324-5p. Stable expression of FBXO11 could abrogate the pro-survival effects of miR-324-5p in CDDP-challenged LCa cells. Together, these findings suggest that miR-324-5p upregulation mediates, at least partially, the CDDP resistance by directly targeting FBXO11 signalling in LCa cells. In-depth elucidation of the molecular basis underpinning miR-324-5p action bears potential implications for mechanism-based strategies to improve CDDP responses in LCa.

To investigate intravoxel incoherent motion (IVIM) tensor imaging of the in vivo human heart and elucidate whether the estimation of IVIM tensors is affected by the complexity of pseudo-diffusion components in myocardium. Methods: The cardiac IVIM data of 10 healthy subjects were acquired using a diffusion weighted spin-echo echo-planar imaging sequence along 6 gradient directions with 10 b values (0~400 s/mm 2). The IVIM data of left ventricle myocardium were fitted to the IVIM tensor model. The complexity of myocardial pseudo-diffusion components was reduced through exclusion of low b values (0 and 5 s/mm 2) from the IVIM curve-fitting analysis. The fractional anisotropy, mean fraction/mean diffusivity, and Westin measurements of pseudo-diffusion tensors (f p and D*) and selfdiffusion tensor (D), as well as the angle between the main eigenvector of f p (or D*) and that of D, were computed and compared before and after excluding low b values. Results: The fractional anisotropy values of f p and D* without low b value participation were significantly higher (P < .001) than those with low b value participation, but an opposite trend was found for the mean fraction/diffusivity values. Besides, after removing low b values, the angle between the main eigenvector of f p (or D*) and that of D became small, and both f p and D* tensors presented significant decrease of spherical components and significant increase of linear components. Conclusion: The presence of multiple pseudo-diffusion components in myocardium indeed influences the estimation of IVIM tensors. The IVIM tensor model needs to be further improved to account for the complexity of myocardial microcirculatory network and blood flow.

Abstract. The purpose of the present study was to investigate the association of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) expression with the histopathological grading of tumors in cerebral glioma. A total of 45 patients with pathologically confirmed cerebral glioma were divided into two groups: a low-grade group (grades I and II, 21 cases) and a high-grade group (grades III and IV, 24 cases). Immunohistochemical staining of tumor samples showed the percentages of tumors expressing VEGF and MMP-9 in the high-grade group to be 95.83 and 75%, respectively, significantly higher than those of the low-grade group (66.67 and 23.81%, P<0.05 and P<0.01, respectively). The magnetic resonance imaging (MRI) results indicated that the peripheral edema index (EI), enhancement percentage (EP), and the maximum diameter of the tumor in the high-grade group were significantly higher than those in the low-grade group (P<0.05, P<0.01, and P<0.05). Moreover, the expression of VEGF and MMP-9 was positively correlated with EI, EP and the maximum diameter of the tumor (P<0.05). Therefore, VEGF and MMP-9 expression were correlated to the invasion of glioma. The association of their expression levels with EI, EP and the maximum tumor diameter indicates that these markers may be used to estimate tumor malignancy for future clinical diagnosis and treatment. IntroductionNeuroglioma, or glioma, is the most common primary tumor of the central nervous system, accounting for approximately 40-50% of all intracranial tumors (1). These tumors are characterized by a high invasive potential and a wide diversity of histological appearance. As with other tumors, one of the crucial steps in invasion is angiogenesis of the peritumoral tissues (2,3). Two primary factors that mediate tumor angiogenesis, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9), have been researched in various tumor types (1-3). These studies show that VEGF and MMP-9 expression varies in the majority of tumor cells and is directly associated with tumor invasion.Recent advances in imaging techniques have increased the use of non-invasive examination in the diagnosis and treatment of glioma. Magnetic resonance imaging (MRI) is one such valuable imaging technique, which has the advantages of non-traumatic, non-ionizing radiation and multiple planar imaging. In combination with other approaches, MRI is capable of visualizing various intracranial lesions (both structural and functional) and detecting the correlation between the major white matter fiber bundle and glioma lesions. Additionally, the complexity of these tumors has generated interest in identifying biomarkers that are capable of aiding in the diagnosis and treatment of gliomas (4). The current study used MRI to determine the correlation of expression of VEGF and MMP-9 with MRI characteristics and clinical pathological grades of cerebral gliomas to aid in clinical treatment and prognosis assessment. Materials and methodsStudy subjects. The study involved...

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PURPOSE: To distinguish hepatocellular carcinoma (HCC) from other types of hepatic lesions with the adaptive multi-exponential IVIM model. METHODS: 94 hepatic focal lesions, including 38 HCC, 16 metastasis, 12 focal nodular hyperplasia, 13 cholangiocarcinoma, and 15 hemangioma, were examined in this study. Diffusion-weighted images were acquired with 13 b values (b = 0, 3, …, 500 s/mm2) to measure the adaptive multi-exponential IVIM parameters, namely, pure diffusion coefficient (D), diffusion fraction (fd), pseudo-diffusion coefficient (Di*) and perfusion-related diffusion fraction (fi) of the ith perfusion component. Comparison of the parameters of and their diagnostic performance was determined using Mann-Whitney U test, independent-sample t test, one-way analysis of variance, Z test and receiver-operating characteristic analysis. RESULTS: D, D1* and D2* presented significantly difference between HCCs and other hepatic lesions, whereas fd, f1 and f2 did not show statistical differences. In the differential diagnosis of HCCs from other hepatic lesions, D2* (AUC, 0.927) provided best diagnostic performance among all parameters. Additionally, the number of exponential terms in the model was also an important indicator for distinguishing HCCs from other hepatic lesions. In the benign and malignant analysis, D gave the greatest AUC values, 0.895 or 0.853, for differentiation between malignant and benign lesions with three or two exponential terms. Most parameters were not significantly different between hypovascular and hypervascular lesions. For multiple comparisons, significant differences of D, D1* or D2* were found between certain lesion types. CONCLUSION: The adaptive multi-exponential IVIM model was useful and reliable to distinguish HCC from other hepatic lesions.